Clinical Trials Register

Summary
EudraCT Number:	2010-020328-23
Sponsor's Protocol Code Number:	EMR200136-532
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-10-28
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2010-020328-23

A.3

Full title of the trial

A three-arm, randomized, double-blind, placebo controlled, multicenter,
phase II study to evaluate the efficacy of Vigantol® oil as add-on
therapy in subjects with Relapsing-Remitting Multiple Sclerosis receiving
treatment with 44 μg tiw of Rebif®

SOLAR

Supplementation of VigantOL® Oil versus Placebo as Add-on in Patients
with Relapsing-Remitting MS receiving Rebif® treatment.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Supplementation of VigantOL® Oil versus Placebo as Add-on in Patients
with Relapsing-Remitting MS receiving Rebif® treatment.

A.3.2

Name or abbreviated title of the trial where available

SOLAR

A.4.1

Sponsor's protocol code number

EMR200136-532

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01285401

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Serono SA - Geneva, an affiliate of Merck KGaA,
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Serono SA - Geneva
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Serono SA - Geneva, an affiliate of Merck
B.5.2	Functional name of contact point	Communication Center Merck KGaA
B.5.3	Address:
B.5.3.1	Street Address	9, Chemin des Mines
B.5.3.2	Town/ city	Geneva
B.5.3.3	Post code	1202
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+496151725200
B.5.5	Fax number	+496151722000
B.5.6	E-mail	service@merckgroup.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vigantol Oel
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Serono GmbH, Germany
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vigantol Oil
D.3.2	Product code	200106 or EMD 28162
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COLECALCIFEROL
D.3.9.1	CAS number	67-97-0
D.3.9.2	Current sponsor code	200109, EMD 28162, 300910
D.3.9.3	Other descriptive name	Cholecalciferol, Vitamin D3
D.3.9.4	EV Substance Code	SUB06794MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	500
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Relapsing-Remitting Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

Relapsing-Remitting Multiple Sclerosis

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy of Vigantol® oil versus placebo as add-on therapy
in subjects with Relapsing-Remitting Multiple Sclerosis receiving
treatment with Rebif®.

E.2.2

Secondary objectives of the trial

• To assess changes on clinical parameters.
• To assess changes in MRI parameters.
• To investigate the safety profile up to the end of the Treatment Period (Week 96),
• To explore pharmacogenetics (PGx), gene expression and circulating biomarkers and to evaluate whether there is a possible relationship to Vigantol® oil treatment outcomes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Diagnosis of a relapsing-remitting form of MS
•Brain and/or spinal MRI with findings typical of MS
•A first clinical event prior to Screening.
•Disease activity
•EDSS score of less than, or equal to 4.0 at Screening.
•Currently treated with interferon-beta-1a 44μg (tiw) sc
•Willingness and ability to comply with the protocol
•Written informed consent

E.4

Principal exclusion criteria

•Pregnancy and lactation period
•Any disease other than MS that could better explain signs and
symptoms.
•Complete transverse myelitis or bilateral optic neuritis.
•Currently receiving or use at any time of monoclonal antibodies,
mitoxantrone, cytotoxic or immunosuppressive therapy (excluding
systemic steroids and adrenocorticotrophic hormone [ACTH]), B cell modulating therapies (e.g. RituxiMab or BelimuMab), total lymphoid irradiation or bone marrow transplantation.
•Use of any cytokine (other than interferon) or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, or any investigational drug or experimental procedure
•Use of oral or systemic corticosteroids or ACTH
•Have experienced a relapse within 30 days before the SD1 visit
•Have abnormalities of Vitamin D related hormonal system other than low dietary intake or decreased sun exposure, i.e. primary
hyperparathyroidism or granulomatous disorders.
•Have an urine calcium/creatinine (mmol/mmol) ratio greater than 1.0 or hypercalcaemia
•Are taking medications that influence Vitamin D metabolism other than corticosteroids, e.g., phenytoin, barbiturates, thiazide diuretics and cardiac glycosides.
•Are taking more than 1000 IU (25 μg) of Vitamin D supplement daily.
•Have conditions with increased susceptibility to hypercalcaemia, e.g., known arrhythmia or heart disease, treatment with Digitalis, or Hydrochlorothiazide and those who suffer from nephrolithiasis.
•Have inadequate liver function
•Moderate to severe renal impairment
•Inadequate bone marrow reserve
•History or presence of serious or acute heart disease such as
uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (NYHA class 3 or 4).
•History or presence of severe depression, history of suicide attempt, or current suicidal ideation.
•Epilepsy or seizures not adequately controlled by treatment.
•Current or past alcohol or drug abuse.
•Any major medical or psychiatric illness (such as psychosis, bipolar disorder) that in the opinion of the Investigator could create undue risk to the subject or could affect adherence with the trial protocol.
•Known contra-indication to treatment with vitamin D
•Known hypersensitivity to interferon or its excipient(s)
•Known hypersensitivity to gadolinium.
•Any other condition that would prevent the subject from undergoing an MRI scan.
•Signs and symptoms suggestive of transmissible spongiform
encephalopathy, or family members who suffer(ed) from such.
•Positive HIV, hepatitis C, or hepatitis B (HBsAg and HBc antibody)
serology (test performed at screening).
•Legal incapacity or limited legal capacity.
•Another current autoimmune disease, except diabetes.

E.5 End points

E.5.1

Primary end point(s)

•Mean number of CUA lesions at week 48
•Proportion of relapse-free subjects at week 96

E.5.1.1

Timepoint(s) of evaluation of this end point

•Mean number of CUA lesions at week 48
•Proportion of relapse-free subjects at week 96

E.5.2

Secondary end point(s)

•Proportion of relapse-free subjects at week 48
•Proportion of subjects free from any EDSS progression at week 48 and 96
•Time to confirmed EDSS progression
•Proportion of subjects free from confirmed EDSS progression at week 48 and 96
•Mean number of new T1 gadolinium-enhancing lesions per subject per scan at week 48 and 96
•Cumulative number of T1 gadolinium enhancing lesions at Week 48 and Week 96
•Cumulative number of new CUA lesions at week 48 and 96
•Mean number of CUA lesions per subject per scan at week 96
•Mean change from baseline in the total volume of T2 lesions at week 48 and 96 (T2 Burden of disease) [mm³]
•Proportion of subjects free from new T1-hypointense lesions (black holes) at week 48 and 96
•Proportion of subjects free from any disease activity: relapse-free, free from confirmed EDSS progression, no new Gd+ lesions and no active T2 lesions at week 48 and 96
•Change in cognitive function at weeks 24, 48, 72 and 96 with respect to baseline as measured by Symbol Digit Modalities Test
•Proportion of T1 gadolinium-enhancing lesions at Study Day 1 (SD1)
that transform into black holes at week 48 and 96
•Percent Brain Volume Change (PBVC) at week 48 and 96 with respect to baseline, and at week 96 with respect to week 48
•Change from baseline in MSFC composite score at Weeks 12, 24, 36, 48, 60, 72, 84 and 96
•Time to first documented relapse
•Annualized relapse rate at Weeks 48 and 96
•Total number of reported relapses at all time points
•Proportion of subjects treated with glucocorticoids due to relapses (during 96 weeks)
•Proportion of subjects free from T1 gadolinium enhancing lesions at Week 48 and Week 96
•Percentage of new T1-hypointense lesions (black holes) at Weeks 48 and 96 within the subgroup of new or enlarging non-enhancing T2
lesions
•Mean change from baseline in total volume of T1 hypointense lesions at Week 48 and Week 96 (in mm³)

E.5.2.1

Timepoint(s) of evaluation of this end point

As described in Section E.5.2

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Austria

Denmark

Estonia

Finland

Germany

Hungary

Italy

Latvia

Lithuania

Netherlands

Norway

Portugal

Switzerland

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

For administrative and safety reporting purposes, the end of the trial will be defined as the date of the final clinical database lock after the last subject has completed the Week 96/Early Termination visit and the safety follow-up visit 4 weeks after, at Week 100. This provides for a single and conservative definition across all trial sites.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

358

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

358

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Not applicable

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-11-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-22

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-05-25

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